Vaginal Cell Research Articles

Heterogeneity in extracellular matrix and immune microenvironment of anterior vaginal wall revealed by single-cell sequencing in women with stress urinary incontinence

Stress urinary incontinence (SUI), characterized by involuntary urine leakage during increased abdominal pressure, remains poorly understood regarding its pathophysiology and treatment. In this study, we utilized single-cell sequencing to analyze the transcriptomic profiles of different cell types in anterior vaginal wall of SUI patients, aiming to explore the heterogeneity of the extracellular matrix (ECM) and immune microenvironment in SUI pathogenesis. Our results identified eleven cell types, including connective tissue cells, immune cells, and glial cells. Specifically, fibroblasts, smooth muscle cells, epithelial cells and T cells displayed transcriptional characteristics highly relevant to SUI pathogenesis. We observed that most cell types participate in ECM metabolism and immune-inflammatory responses, indicating a synergistic role of multiple vaginal cell types in SUI. Furthermore, altered intercellular communication, particularly between fibroblasts and T cells, was noted in SUI. This study provides novel single-cell insights into SUI and identifies potential biomarkers and therapeutic targets for future research.

Vaginal Mucosal Melanoma Cell Activation in Response to Photon or Carbon Ion Irradiation

PurposePrimary gynecological melanomas are uncommon with lower survival rates compared to cutaneous melanomas. Although melanocytes have been identified in a variety of mucosal membranes, little is known about their interactions or roles inside the mucosa layer. Melanin is a common pigment in nature and is endowed with several peculiar chemical, paramagnetic, and semiconductive characteristics. One of its latest explored functions is its interaction with ionizing radiation as a protective mechanism as well as its implication in the metastatic cascade of tumor cells. Materials and MethodsIn this work, we analyzed in vitro the effects of different doses of photon and carbon ion irradiation on dendrite formation, pigmentation, migration, and invasion abilities of human mucosal melanoma cells of the vagina. We evaluated the morphology and melanin production of HMV-II cells exposed to photon and carbon ion beams with single doses between 0.5 and 10 Gy. ResultsOur results showed that irradiation induces dendrite formation or elongation and pigmentation in HMV-II cells in a dose-type-dependent and radiation-type-dependent way but also a decrease in cell motility. ConclusionThe present study describes for the first time an induction of dendritic formation, melanin production, and alterations in migration and invasion abilities by low-linear energy transfer and high-linear energy transfer radiation in human mucosal melanoma cells, suggesting a radioprotective response to further possible exposures increasing the radioresistance of these cells.

Zuogui Pills Improve the Learning and Memory Ability of Brain-Aging Mice through the Estrogen Receptor ERα Methylation Pathway.

Sex hormones are important factors in maintaining brain function and acting as brain protectors. Recent research suggests that neuronal damage in brain aging may be linked to the methylation of the estrogen receptor α (ERα). However, the mechanism of Zuogui Pills (ZGW) in brain-aging ERα DNA methylation and neuronal repair remains unknown. D-galactose-induced ovary removal mice were used as a model of aging. Changes in estrous cycle were detected in mice by vaginal cell smear. Animal behavior tests, including the Morris water maze (MWM) and new object recognition (NOR) test, were conducted. Hematoxylin-eosin (HE) and Nissl-staining were carried out to assess hippocampal neurogenesis. Enzyme-linked immunosorbent assay (ELISA) was performed for 5- methylcytosine methylation levels, and immunohistochemistry (IHC) and western blotting (WB) experiments were performed to assess ERα/DNA methyltransferase 1 (DNMT1) expression after ZGW treatment. Finally, bisulfite sequencing PCR (BSP) analysis was performed to identify methylated differentially expressed estrogen receptor 1 (ESR1) gene in D-gal-induced senescent neurons before and after ZGW treatment. We found that ERα methylation was involved in the delayed brain ageing process of ZGW. Mechanistically, ZGW can improve the learning and memory ability of brain-aging mice, reduce the expression of 5-methylcytosine (5-mc) in serum, increase the amount of ERα, inhibit the expression of DNMT1, and significantly reduce methylated expression of the ESRI gene. Our data suggested that ZGW slowed down D-gal-induced brain aging in mice, and these results showed that ZGW is beneficial for aging. It may be used for neuronal protection in aging.

Detection, Optimization, Characterization, and Cytotoxic Effect of Vaginolysin Extracted from Gardnerella Vaginalis Isolated from Iraqi Women Who Had Abortions

Objective: The goal of this study is the detection of the gen that responsible for production the vaginolysin toxin, discovered the optimal condition for produce vaginolysin, purification and characterization of the toxin and show the cytotoxic effect of vaginolysin on VK2cell and HeLa cell. Methods: Among 592 specimens isolated from pregnant women suffering from vaginal inflammation and threatened with abortion(these women is suffering from strong pain in the cervical region), only 62 of isolates identified as G vaginalis. From Baghdad teaching hospital. detection of the gen that responsible for production the vaginolysin toxin. study of the optimal condition to produce vaginolysin. the purification of the toxin by using ammonium sulfate, ion exchange chromatography and gel filtration, toxin characterization of pH and temperature activity and stability, the study of cytotoxic effect of vaginolysin on VK2 and HeLa cells. Result: The optimal condition to produce the toxin is pH level in 4, best temperature is 37 0C, the best media is TSB broth , and the best hours is 24hr. . The best range for precipitation saturation ratio 50%. ion exchanges have specific activity 4 mg. gel filtrations show an increase in the specific activity of purified toxin (10U/mg). the characterization done by pH and temperature,Vaginolysin was active in 0.5 U/ mL at pH 7, and stable in pH 7 activity, the best temperature for vaginolysin activity is 0.5 U/mL at 37°C and maximum stability was recorded at 37°C . the cytotoxic effect of the toxin on VK2 cell observed the viability ratio 69.98%, at higher toxin concentration, while the result for HeLa cell viability ratio 38.77%, at higher toxin concentration. Conclusion: vaginolysin cause lysis of vaginal cell and cervical cell may lead to abortion, the killing ratio increase by increasing the concentration of the toxin and the effect of the toxin on HeLa cell is more than on VK2 cell.

Intravaginally CpG-ODN and Salmonella enteritidis on TLR21, cytokines, and AvBD10 gene expressions in the reproductive tract of native chicken.

Salmonella enterica subsp. enterica serovar Enteritidis (SE) is a global concern for the poultry industry due to its association with foodborne illnesses. The transmission occurs through the transovarial route which initiates from colonization in oviducts and ascending to ovaries. Though there are studies on cytosine-phosphate-guanine oligodeoxynucleotide (CpG-ODN) and the increase of innate immune response, there is limited research on the intravaginal treatment using CpG-ODN. Previous studies have shown that stimulating CpG-ODN can induce the production of antimicrobial peptide avian beta-defensins (AvBDs) in vaginal cell cultures, there is limited information on the use of intravaginal treatment to induce the innate immune system, particularly in the Kampung Unggul Balitbangtan (KUB-1) chickens (Gallus gallus domesticus). This study investigates the impact of intravaginal CpG-ODN stimulation on the innate immune response in KUB-1 chicken ovaries and oviducts when challenged to SE. A total of 39 KUB-1 chickens were divided into four groups namely T1 (treated with CpG-ODN, n=12), T2 (SE group, n=12), T3 (CpG-ODN and SE, n=12), and Control (without CpG-ODN and SE, n=3). Chickens were observed from day 1 to 4 post-intravaginal (PI) inoculation. The results suggest that intravaginal CpG-ODN treatment modulates AvBD10 production through toll-like receptor (TLR)21, with interleukin (IL)1B and IL10 playing reciprocal roles, providing insights into the potential of this treatment to prevent transovarial Salmonellosis in poultry. The novelty of this study adds valuable insights to the current body of knowledge.

Estrus detection on different thoroughbred crossbreed horses with vaginal smear and vaginal acidity method

Abstract Breeding manipulation season in racehorses is required to ensure the birth at the specific period (August-December), which will maximize the foal’s age when participating in their first race (July). Therefore, it is important to time the mating of mares using highly accurate estrus detection methods. This research was conducted to identify the differences data using vaginal smear and pH vagina of Thorougbred crossbreed mares in estrus and anestrus phases. Fifteen multiparous mares were conducted with a period of estrus of 19-22d. The result data showed significant differences (P<0.05) in the vaginal cell distribution patterns at each phase of the estrus cycle. The superficial cells predominate (92.43±5.14%) in the estrus phase while significant parabasal cells (87.89±3.09%) predominate in the anestrus phase. The results also showed a significant difference (P<0.05) in vaginal pH which was much more alkaline (8.71±0.25) in the estrus phase while more significantly acidic-normal (6.02±0.26) in the anestrus phase. However, the results showed no difference both in vaginal smear and pH vagina based on pedigree group. Finally, the pattern of superficial cells being more common and vaginal pH levels being higher during estrus may offer a new way to find out when an equine is in estrus.

Fungal burden, dimorphic transition and candidalysin: Role in Candida albicans-induced vaginal cell damage and mitochondrial activation in vitro.

Candida albicans (C. albicans) can behave as a commensal yeast colonizing the vaginal mucosa, and in this condition is tolerated by the epithelium. When the epithelial tolerance breaks down, due to C. albicans overgrowth and hyphae formation, the generated inflammatory response and cell damage lead to vulvovaginal candidiasis (VVC) symptoms. Here, we focused on the induction of mitochondrial reactive oxygen species (mtROS) in vaginal epithelial cells after C. albicans infection and the involvement of fungal burden, morphogenesis and candidalysin (CL) production in such induction. Bioluminescent (BLI) C. albicans, C. albicans PCA-2 and C. albicans 529L strains were employed in an in vitro infection model including reconstituted vaginal epithelium cells (RVE), produced starting from A-431 cell line. The production of mtROS was kinetically measured by using MitoSOX™ Red probe. The potency of C. albicans to induced cell damage to RVE and C. albicans proliferation have also been evaluated. C. albicans induces a rapid mtROS release from vaginal epithelial cells, in parallel with an increase of the fungal load and hyphal formation. Under the same experimental conditions, the 529L C. albicans strain, known to be defective in CL production, induced a minor mtROS release showing the key role of CL in causing epithelial mithocondrial activation. C. albicans PCA-2, unable to form hyphae, induced comparable but slower mtROS production as compared to BLI C. albicans yeasts. By reducing mtROS through a ROS scavenger, an increased fungal burden was observed during RVE infection but not in fungal cultures grown on abiotic surface. Collectively, we conclude that CL, more than fungal load and hyphae formation, seems to play a key role in the rapid activation of mtROS by epithelial cells and in the induction of cell-damage and that mtROS are key elements in the vaginal epithelial cells response to C. albicans.

Infertility in POMC-deficient mice

The pro-opiomelanocortin (POMC) gene is expressed in the hypothalamus and pituitary and its product is cleaved into several peptides including the melanocyte stimulating hormones (α, β, or γ-MSH), adrenocorticotropic hormone (ACTH), and beta-endorphin. Alpha-MSH is involved in regulating appetite, sexual behavior, and melanin, while ACTH regulates secretion of glucocorticoids from the adrenal cortex. Humans who have a POMC mutation either produce an abnormally short version of POMC or are missing the protein completely and therefore lack these hormones. This has biological consequences including red hair and fair skin, early-onset obesity (due to severe hyperphagia), and potentially hypothyroidism, hypogonadism, and infertility. Many of these same effects are seen with mice containing this deficiency. We are interested in studying infertility through a mouse model of hypothalamic-specific POMC-deficiency. These mice also experience early-onset obesity and infertility. Estradiol is a key reproductive hormone that is essential for fertility. POMC deficiency may lead to hypogonadism, which can cause low levels of estrogen so we hypothesize that POMC-deficient mice have reduced estrogen levels, which may contribute to their infertility. To test this hypothesis, we will measure estrogen levels in POMC-deficient mice at different stages of the estrus cycle using an estradiol ELISA kit. We expect the POMC-deficient mice to have lower estrogen levels than control mice. We also plan to use liquid chromatography mass spectrometry (LC-MS) to measure estrogen levels. Before collecting the blood samples, vaginal cell samples are obtained and viewed under a microscope to analyze the ratio of cells and determine which stage the females were in—proestrus, estrus, metestrus, or diestrus. Blood samples are then collected into 1.5 mL microcentrifuge tubes with 10 microliters of 0.5 M EDTA to prevent blood clotting. After blood is collected, it is centrifuged at 2,000 g for 20 minutes at 4 degrees Celsius. The plasma is then stored at -80 degrees Celsius until analysis. Based on preliminary results we expect the POMC deficient mice to have reduced estrogen and/or altered levels throughout the cycle. So far, our results have indicated that POMC-deficient female mice have abnormal estrus cycles and also reduced uterine weights. The conclusions from this study will help us understand more about the causes of infertility in POMC-deficient mice, which may also lead to greater understanding on how to treat humans with infertility due to a POMC mutation. Support for this research was provided by IRACDA grant NIHK12GM111725 to Z.T. and UVU Scholarly Activities Grant to A.G. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

The Validity of Immunohistochemistry in Detecting Microsatellite Instability in Pediatric Solid Neoplasms

Abstract Background: The DNA mismatch repair (MMR) is the biological pathway that plays a key role in maintaining genomic stability during DNA replication and recombination. The value of MMR pathway is under investigation in pediatrics’ solid tumors. Aims: In this research work, we investigated the proteins involved in the oncogenesis of pediatric solid neoplasms and detect these proteins in a representative cohort sample of Saudi pediatric cases under the bioinformatic networking technique. We also described the MLH1, BRAF, p53, proliferating cell nuclear antigen, and PMS2 along with MSH2-MSH6 antibodies to be a diagnostic immunohistochemistry (IHC) panel for identifying MMR mutations. This research will open the new doors for advanced research on proteins involved in the oncogenesis of pediatric solid neoplasms. The hypotheses were tested on a sample of solid malignancies and IHC results were reported. Material and Methods: The study was conducted in different institutions in Saudi Arabia. The inclusion criteria required enrolling biopsies of solid neoplasms or resected solid malignant neoplasms presented to the laboratories in the participating institutions of all pediatric patients (aging from 0 to 14 years). The specimens were examined microscopically utilizing Hematoxylin and Eosin stain as well as the utilization of MMR proteins immunohistochemistry (IHC), and PNCA. Results: The qualitative assessment showed that IHC diagnosis yielded positive results with ≥80% of positive cells (intact) for MMR proteins (MSH2, MSH6, PMS2, and MLH1). The PCNA protein was absent only in vaginal germ cell tumor and metastatic medulloblastoma. Conclusion: In our sample, we have found that there is an intact MMR proteins expression. Also, the IHC technique presents accuracy and ability as a diagnostic technique for identifying the different types of pediatric cancers. The MMR protein panel accompanied with PCNA panels holds additional value, as it helps reduce dependency solely on MMR protein expressions.

The risk of vaginal, vulvar and anal precancer and cancer according to high-risk HPV status in cervical cytology samples.

High-risk human papillomavirus (hrHPV) is the cause of virtually all cervical cancers, most vaginal and anal cancers, and some vulvar cancer cases. With HPV testing becoming the primary screening method for cervical cancer, understanding the link between cervical hrHPV infection and the risk of other anogenital cancers is crucial. We assessed the risk of vulvar, vaginal and anal cancer and precancer (VIN2+, VaIN2+ and AIN2+) in a prospective cohort study including 455,349 women who underwent cervical hrHPV testing in Denmark from 2005 to 2020. We employed Cox proportional hazard models, adjusting for age, calendar year and HPV vaccination status, and estimated hazard ratios (HRs) and 95% confidence intervals (CI). We used the Aalen Johansen estimator to calculate the absolute risks of VIN2+, VaIN2+ and AIN2+. In total, 15% of the women were hrHPV positive at baseline. A positive cervical hrHPV test was associated with increased incidence of vulvar, vaginal and anal squamous cell carcinoma (SCC). Five-year risk estimates of VIN2+, VaIN2+ and AIN2+ among hrHPV-positive women (0.45%, 0.14% and 0.12%) were higher than among hrHPV-negative women (0.14%, 0.01% and 0.05%). Particularly high risk was observed among the hrHPV-positive women of the oldest age, with a history of anogenital precancer and those not HPV vaccinated. In conclusion, our study confirms the association between cervical hrHPV infection and non-cervical anogenital precancers and cancers. Currently, no established risk threshold or guidelines for follow-up. As HPV testing becomes the primary method for cervical cancer screening, future data will help define high-risk groups and acceptable risk thresholds.

Subtotal hysterectomy causes fewer long-term detrimental effects on ovary tissues than total hysterectomy.

Hysterectomy is the basic surgical procedure of gynecological surgery. Traditionally, it is divided into total hysterectomy (TH) and subtotal hysterectomy (STH) according to the scope of surgery. The ovary is a dynamic organ appended with the uterus, and the uterus provides vascular supply to the developing ovary. However, the long-term impacts of TH and STH on ovary tissues need to be evaluated. In this study, rabbit models of different ranges of hysterectomy were successfully created. The estrous cycle of animals was determined by vaginal exfoliated cell smear 4 months after the operation. The apoptosis rate of ovarian cells in each group was determined by flow cytometry, and the morphology of ovarian tissue and granulosa cells in the control group, triangular hysterectomy group and total hysterectomy group were observed under microscope and electron microscope, respectively. After total hysterectomy, the apoptotic events in ovarian tissues were significantly increased when compared to the sham and triangle hysterectomy group. Increased apoptosis was accompanied with the morphological changes and disrupted organelle structures in ovarian granulosa cells. The follicles in the ovarian tissue were dysfunctional and immature, with more atretic follicles being observed. In contrast, ovary tissues in triangular hysterectomy groups showed no obvious defects on the morphology of ovarian tissue and granulosa cells. Our data suggest that subtotal hysterectomy may serve as an alternative to total hysterectomy, with fewer long-term detrimental effects on ovary tissues.

Dysregulated wound healing in the pathogenesis of urogynecologic mesh complications

To test the hypothesis that dysregulated wound healing is associated with Urogynecologic mesh complications, we collected vaginal cell secretions using vaginal swabs after polypropylene mesh implantation in patients with (N = 39) and without (N = 40) complication. A customized multiplex immunoassay measured markers of inflammation (MCP-1, IGFBP-1, IL-2, IL-10, IL-17, PDGF-BB, bFGF, IL-1b, IL-6, IL-12p70, TNF-α), neuroinflammation (IL-1RA, TGF-β, IL-15, IL-18, IL-3, M-CSF), angiogenesis (VEGF), and matrix proteins (fibronectin, tenasin c, thrombospondin-2, lumican) between groups. Patients with complications were younger, heavier, implanted with mesh longer, and more likely to be ever smokers. A 5 kg/m2 BMI increase and ever-smoking were associated with a 2.4-fold and sixfold increased risk of complication, respectively. Patients with the highest tertile of bFGF, fibronectin, thrombospondin-2, TNF-β, or VEGF had an odds ratio (OR) of 11.8 for having a mesh complication while ≥ 3 elevated had an OR of 237 while controlling for age, BMI, and smoking. The highest tertile of bFGF, thrombospondin-2, and fibronectin together perfectly indicated a complication (P < 0.0001). A receiver-operator curve for high bFGF, thrombospondin-2, and fibronectin showed excellent discrimination between complications and controls (AUC 0.87). These data provide evidence of dysregulated wound healing in mesh complications. Modifiable factors provide potential targets for patient counseling and interventions.

Postnatal feeding with high-fat combined with high-glucose diet induces precocious puberty in Sprague‒Dawley rat pups

With economic development and overnutrition, including high-fat diets (HFD) and high-glucose diets (HGD), the incidence of obesity in children is increasing, and thus, the incidence of precocious puberty is increasing. Therefore, it is of great importance to construct a suitable animal model of overnutrition-induced precocious puberty for further in-depth study. Here, we fed a HFD, HGD, or HFD combined with a HGD to pups after P-21 weaning, while weaned pups fed a normal diet served as the control group. The results showed that HFD combined with a HGD increased the body weight (BW) of weaned rat pups. In addition, a HFD, HGD, and HFD combined with a HGD lowered the age at which vaginal opening occurred and accelerated the vaginal cell cycle. Furthermore, a HFD combined with a HGD increased the weight of the uterus and ovaries of weaned rat pups. Additionally, a HFD combined with a HGD promoted the development of reproductive organs in weaned female rat pups. Ultimately, a HFD combined with a HGD was found to elevate the serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), leptin, adiponectin, and oestradiol (E2) and increase hypothalamic GnRH, Kiss-1, and GPR54 expression levels in weaned female rat pups. The current study found that overnutrition, such as that through a HFD combined with HGD, could induce precocious puberty in weaned female rat pups. In addition, a rat model of overnutrition-induced precocious puberty was established.

Metronidazole Treatment Failure and Persistent BV Lead to Increased Frequencies of Activated T- and Dendritic-Cell Subsets.

Metronidazole (MDZ) treatment failure and bacterial vaginosis (BV) recurrence rates are high among African women. This cohort study identified genital immune parameters associated with treatment response by comparing vaginal microbiota and immune cell frequencies in endocervical cytobrushes obtained from 32 South African women with symptomatic BV pre- and post-metronidazole treatment. Cervical T- and dendritic-cell subsets were phenotyped using multiparameter flow cytometry and the composition of vaginal microbial communities was characterized using 16S rRNA gene sequencing. MDZ treatment led to a modest decrease in the relative abundance of BV-associated bacteria, but colonization with Lactobacillus species (other than L. iners) was rare. At 6 and 12 weeks, MDZ-treated women had a significant increase in the frequencies of CCR5+ CD4+ T cells and plasmacytoid dendritic cells compared to the pre-treatment timepoint. In addition, MDZ non-responders had significantly higher frequencies of activated CD4 T cells and monocytes compared to MDZ responders. We conclude that MDZ treatment failure was characterized by an increased expression of activated T- and dendritic-cell subsets that may enhance HIV susceptibility. These data suggest the need to further assess the long-term impact of MDZ treatment on mucosal immune response and the vaginal microbiota.

Outcome and late effects of patients treated for childhood vaginal malignant germ cell tumors.

Vaginal malignant germ cell tumors (MGCT) are rare, occurring in children less than 2years old and raise the question of the optimal local treatment. We included children treated for vaginal MGCT according to the French TGM-95/2013 regimen. Patients were classified as standard risk (SR: localized disease and alpha-fetoprotein (AFP)<10,000ng/mL) or high risk (HiR: metastatic and/or AFP>10,000ng/mL) and were treated, respectively, with three to five VBP (vinblastine-bleomycin-cisplatin) or four to six VIP (etoposide-ifosfamide-cisplatin), followed by conservative surgery and/or brachytherapy in case of post-chemotherapy residuum. Fourteen patients were included (median age=12months), of which six (43%) were classified as HiR. AFP levels were normalized after first-line chemotherapy in all cases but one. A vaginal post-chemotherapy residuum (median size=8mm, range: 1-24mm) was observed in 13/14 patients, treated by complete resection in seven of 13 (viable cells in three of seven), incomplete resection in four of 13 (viable cells in two of four), with adjuvant brachytherapy in two of 13, and exclusive brachytherapy in two of 13 (viable cells in one of six). Among the six patients with viable disease, four patients received adjuvant chemotherapy. One patient (SR) experienced immediate postoperative relapse despite presenting no viable residual cells and was treated with four VIP cycles and brachytherapy. At last follow-up (median=4.6years, range: 0.5-16), all patients were alive in complete remission. Five patients suffered from vaginal sequelae with synechiae and/or stenosis (of whom four had undergone brachytherapy). Childhood vaginal MGCTs show a highly favorable prognosis with risk-adapted chemotherapy and local treatment of post-chemotherapy residuum (preferably by conservative surgery with partial vaginectomy). Brachytherapy could be an alternative when conservative surgery is not deemed possible or in cases of incomplete resection with residual viable cells.

Late Cervical And Vaginal Clear Cell Adenocarcinoma In Women Exposed In Utero To Diethylstilbestrol: Evaluation And Screening.

We aimed to evaluate the risk of cervical and vaginal clear cell adenocarcinoma (CCA) in women, aged 50 years or more, exposed in utero to diethylstilbestrol (DES) and contribute to a reevaluation of the recommendations for cervical and vaginal cancer and pre-cancer screening for these women. We carried out a retrospective review for patients received in a cancer institute. Two cohorts were consecutively studied, the first from 1970 to 2003 and the second from 2004 to 2021, and then linked. During the first period, we observed 61 CCA cases, with a mean age at diagnosis of 23 years (7-42), 36 (59%) following DES exposure in utero. During the second period, we found 27 cases, with one case of DES exposure (4%) for a women diagnosed at the age of 40 years. The mean age of the second cohort was 38 years (14-79). For the seven women aged 50 years or more at the time of CCA diagnosis, DES exposure was excluded for five and considered unlikely for the other two. In total, 88 cases of cervical or vaginal CCA were observed over a period of 51 years in a cancer center. The 37 cases associated with DES exposure represented approximatively one third of the CCA related to DES expected in France. DES exposure was improbable for the seven cases of CCA for women aged 50 years or more. These results do not support the hypothesis of late cervical or vaginal CCA in women exposed to DES in utero and indicate the need for larger multicentric studies. For the present, we propose specific screening for women exposed to DES in utero in terms of : 1) methods: association of cytology and hrHPV testing, with cervical and vaginal sampling, 2) timing : annual, or without exceeding a three-year interval, continuing after 65 years of age and after hysterectomy.

758P Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic vulvar and vaginal squamous cell carcinoma: Subgroup analysis of the PEVOsq basket trial

758P Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic vulvar and vaginal squamous cell carcinoma: Subgroup analysis of the PEVOsq basket trial

Xenobiotic metabolites modify immune responses of the cervicovaginal epithelium: potential mechanisms underlying barrier disruption.

Xenobiotic metabolites are exogenous biochemicals that can adversely impact reproductive health. We previously identified xenobiotics in cervicovaginal fluid during pregnancy in association with short cervix. In other organ systems, xenobiotics can modify epithelial barrier function. We hypothesise that xenobiotics dysregulate epithelial cell and macrophage immune responses as a mechanism to disrupt the cervicovaginal barrier. In vitro cell culture system. Laboratory within academic institution. Vaginal, ectocervical and endocervical epithelial cell lines and primary macrophages. Cells were treated with diethanolamine (2.5 mM), ethyl glucoside (5 mM) or tartrate (2.5 mM) for 24 h. Cytokines and matrix metalloproteinases were measured in cell supernatants (n = 3 per condition). One-way analysis of variance (ANOVA) with Dunnett's test for multiple comparisons was performed. Diethanolamine induces inflammatory cytokines, whereas ethyl glucoside and tartrate generally exert anti-inflammatory effects across all cells. Diethanolamine increases interleukin 6 (IL-6), IL-8, interferon γ-induced protein 10 kDa (IP-10), growth-regulated oncogene (GRO), fractalkine, matrix metalloproteinase 1 (MMP-1), MMP-9 and MMP-10 (p < 0.05 for all), factors involved in acute inflammation and recruitment of monocytes, neutrophils and lymphocytes. Ethyl glucoside and tartrate decrease multiple cytokines, including RANTES and MCP-1 (p < 0.05 for all), which serve as chemotactic factors. Vaginal cells exhibit heightened inflammatory tone compared with cervical cells and macrophages, with a greater number of differentially expressed analytes after xenobiotic exposure. Xenobiotic metabolites present in the cervicovaginal space during pregnancy modify immune responses, unveiling potential pathways through which environmental exposures may contribute to the pathogenesis of cervical remodelling preceding preterm birth. Future work identifying xenobiotic sources and routes of exposure offers the potential to modify environmental risks to improve pregnancy outcomes.

Mesh and layered electrospun fiber architectures as vehicles for Lactobacillus acidophilus and Lactobacillus crispatus intended for vaginal delivery

Bacterial vaginosis (BV) is a recurrent condition that affects millions of women worldwide. The use of probiotics is a promising alternative or an adjunct to traditional antibiotics for BV prevention and treatment. However, current administration regimens often require daily administration, thus contributing to low user adherence and recurrence. Here, electrospun fibers were designed to separately incorporate and sustain two lactic acid producing model organisms, Lactobacillus crispatus (L. crispatus) and Lactobacillus acidophilus (L. acidophilus). Fibers were made of polyethylene oxide and polylactic-co-glycolic acid in two different architectures, one with distinct layers and the other with co-spun components. Degradation of mesh and layered fibers was evaluated via mass loss and scanning electron microscopy. The results show that after 48 h and 6 days, cultures of mesh and layered fibers yielded as much as 108 and 109 CFU probiotic/mg fiber in total, respectively, with corresponding daily recovery on the order of 108 CFU/(mg·day). In addition, cultures of the fibers yielded lactic acid and caused a significant reduction in pH, indicating a high level of metabolic activity. The formulations did not affect vaginal keratinocyte viability or cell membrane integrity in vitro. Finally, mesh and layered probiotic fiber dosage forms demonstrated inhibition of Gardnerella, one of the most prevalent and abundant bacteria associated with BV, respectively resulting in 8- and 6.5-log decreases in Gardnerella viability in vitro after 24 h. This study provides initial proof of concept that mesh and layered electrospun fiber architectures developed as dissolving films may offer a viable alternative to daily probiotic administration.

Comparison of the Efficacy of Vaginal Hyaluronic Acid to Estrogen for the Treatment of Vaginal Atrophy in Postmenopausal Women: A Systematic Review.

Topical estrogen is effective for treating postmenopausal vaginal atrophy. However, there is a potential risk of estrogen-related adverse effects. There is a need for finding effective non-hormonal treatment for vaginal atrophy. The topical application of moisturising agents, such as hyaluronic acid (HA), represents a promising non-hormonal treatment for the relief of vaginal atrophy. This study aimed to summarize the evidence regarding the efficacy of topical HA compared to topical estrogen in postmenopausal women with vaginal atrophy. The literature search covered English-published studies from database inception till February 2023. The search included the electronic databases of MEDLINE/PubMed, Cochrane Library, Web of Science, ProQuest, and Scopus, using the terms "Hyaluronic Acid" AND "Postmenopause" AND "Vagina" AND "Atrophy". Due to the diversity in reporting outcomes, meta-analysis was not feasible. A narrative synthesis with a systematic approach was conducted by vote counting of studies that included a direct comparison between topical HA and topical estrogen. Six studies were included. Intra-group comparisons showed that both interventions were significantly effective in alleviating the symptoms of vaginal atrophy and dyspareunia as well as improving vaginal pH and cell maturation index. However, inter-group comparisons in most studies showed that estrogen was superior to HA in relieving vaginal symptoms and improving vaginal pH, dyspareunia, and the cell maturation index. There is no evidence to show the superiority of HA to estrogen in the treatment of postmenopausal vaginal atrophy. However, the therapeutic efficacy of HA seems to be comparable to estrogen and considering its safety, HA can be used as an alternative to estrogen in patients who do not want to use estrogen. The available studies have several limitations, and the reporting of outcomes was considerably heterogeneous.